| Project/Area Number |
04454118
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Applied veterinary science
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| Research Institution | OBIHIRO UNIVERSITY OF AGRICULTURE AND VETERINARY MEDICINE |
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Principal Investigator |
NISHIMURA Masakazu Obihiro University of Agriculture and Veterinary Medicine, Department of Veterinary Pharmacology, Professor., 畜産学部, 教授 (50011995)
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| Co-Investigator(Kenkyū-buntansha) |
SATOH Eiki Obihiro University of Agriculture and Veterinary Medicine, Department of Veterin, 畜産学部, 助手 (50178711)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1992: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Keywords | D-penicillamine / dithiothreitol / N-ethylmaleimide / thyroxine / d-tubocurarine / mouse / myathenic syndrome / 胸腺 / 筋力試験 / thyroxine / D-penicillamine |
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| Research Abstract |
The purpose of this research was to analyze and discuss the mechanism by which the myathenic syndrome appears in mice chronically administered some chemicals including d-penicillamine (DPN), dithiothreitol (DTT). N-ethylmaleimide (NEM). This trial examined a possible role of hypertrophy of the thymus on the incidence of this syndrome. Thyroxine (TRX) was administered to test this possibility. Both DPN and TRX elevated the sensitivity of the mouse to d-tubocurarine (dTc) measured as LD_<50>. This effect did not depend on the sex. TRX was more potent in this effect than DPN.DPN administered simultaneously with TRX reduced the effect of TRX alone. Thus, an excess amount of TRX secreted may have a poor possibility to accelerate the effect of DPN even if it may cause the thymokesis. TRX actually increased the weight of thymus in female mice. However, the sensitization to dTc did not depend on the sex. Chronic treatment of the mouse with DTT or NEM accelerated selectively the sensitivity of
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neuromuscular transmission in the diaphragm in vitro, showing that the change did not derive from characteristic autoimmune disease. Female mice administered TRX alone or combined with DPN showed the muscle weakness, increased the weight of thymus, accumulated abdominal dropsy, and increased the sensitivity to dTc both in vivo and in vitro. However, DPN never accelerated all of these effects of TRX.Chronic treatment with DPN alone did not affect the sensitivity of nerve-muscle preparations to dTc in vitro while it sensitized to dTc in vivo.Thus, the present observations did not support both ideas that DPN may be causal in the incidence of myathenic syndrome and that TRX may accelerate the effect of DPN via making hypertrophic the thymus in the mouse. It was speculative that the hypertrophic diseases of the thymus as thymoma may be important to incidence of the myathenic syndrome on the process that the thymokesis accelerates the effect of DPN inducing the syndrome even if the induction of the myathenia gravis by DPN in man relates to the thymokesis. Less
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